My research activity involves the induction of salivary IgA antibodies against a virulence determinant of Streptococcur muturs. Using recombinant DNA technology, the saliva-binding region (SBR) of the S. mutans AgI/II adhesin was expressed in an avirulent strain of Salmonella typhimurium, which can be used as a live antigen-delivery system for oral immunization. After oral administration, S. typhimurium selectively colonizes the gut-associated Iymphold tissues, where secretory IgA antibody responses are initiated. This vaccination system was tested in mice which elicited substantial levels of secretory IgA antibodies to SBR in saliva. However, a higher salivary IgA response to SBR was observed when SBR polypeptide was co-expressed in S. typhimurium with non-toxic A2/B subunits of cholera toxin. In an effort to further investigate the immunoecnhancing activity of the cholera toxin B subunit (CTB)in antigen-delivery systems, studies were performed concerning the effect of CTB when conjugated to the surface of liposomes containing the SBR antigen. The rationale is that the affinity of CTB for GMI ganglioside receptors may target the entry of this antigen-delivery system into the gut-associated lymphoid tissues, thereby resulting in increased SBR antigen uptake and augmented immune responses. Recombinant (r) CTB was conjugated to the outer surface of liposomes containing SEIR, by means of a thiolhcr bond. 0ra1 immunization studies in mice resulted in significant higher immune responses to SBR induced by the rCTB-conjugated liposomes versus plain liposome-carriers of SBR, indicating usefulness of this antigen delivery system for oral immnunization. Recently, studies have been initiated to investigate the possible mechanisms contributing in the effective of the rCTB-conjugated lipo somes as an oral vaccination strategy. In this regard, the direct effect of these liposomes to the intestinal epithelium as well as immune cells is studies.